The proposed study is designed to probe the molecular structure of ferritin and relate the structure to its capacity to retain large amounts of iron, and to its overall function in iron metabolism. The mechanism of assembly of ferritin subunits will be studied in our effort to elucidate the manner in which the subunits aggregate in vivo, and the possible regulatory effects this process may have on ferritin biosynthesis. Attempts will be made to determine the forces that unite the subunits, and to define their chemical nature, and to modify the protein. We also hope to ascertain the extent of ferritin heterogeneity and the origin of this heterogeneity. The formation of oligomers of whole ferritin molecules will also be studied. Environmental perturbants will be employed and their effects on the physicochemical properties of the protein will be determined. Ultimately we hope to gain insight into the mechanism by which iron is incorporated into, stored, and subsequently released by the protein, and to further the understanding of the overall scheme of iron metabolism. Ferritins from human liver and spleen, rat liver and horse spleen will be compared.